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Major Form (major + form)

Distribution by Scientific Domains
Life Sciences41%
Medical Sciences33%
Chemistry11%
Humanities and Social Sciences8%
2 Other Domains7%
Distribution within Life Sciences
Neuroscience31%
Cell & Molecular Biology12%

Selected Abstracts

Stopping petrol sniffing in remote Aboriginal Australia: key elements of the Mt Theo Program

DRUG AND ALCOHOL REVIEW, Issue 3 2006
KARISSA PREUSS Manager
Abstract Petrol sniffing is a major form of substance misuse in Aboriginal communities across Australia. This practice has detrimental effects on the health and wellbeing of individual sniffers, their families, communities and wider society. There are few examples of programmes that have successfully stopped petrol sniffing. This paper looks at the Mt Theo Program, regularly cited as ,the success story' in petrol sniffing interventions. The aim of this paper is to demonstrate key elements that have contributed towards Mt Theo Program's rare achievement: (1) initially, a multi-faceted approach including an outstation and youth programme, (2) community-initiated, operated, owned basis of the organisation, which incorporates (3) strong partnership between Indigenous and non-Indigenous team members and (4) an ability to operate beyond crisis intervention. [source]

Differential Pulse Voltammetric Determination of Selenocystine Using Selenium-gold Film Modified Electrode

ELECTROANALYSIS, Issue 17 2005
Yan Bai
Abstract Differential pulse voltammetric determination of selenocystine (SeC) using selenium-gold film modified glassy carbon electrode ((Se-Au)/GC) is presented. In 0.10,mol,L,1 KNO3 (pH,3.20) solution, SeC yields a sensitive reduction peak at ,740,mV on (Se-Au)/GC electrode. The peak current has a linear relationship with the concentration of SeC in the range of 5.0×10,8,7.0×10,4,mol,L,1, and a 3, detection limit of SeC is 3.0×10,8,mol,L,1. The relative standard deviation of the reduction current at SeC concentration of 10,6,mol,L,1 is 3.88% (n=8) using the same electrode, and 4.19% when using three modified electrodes prepared at different times. The content of SeC in the selenium-enriched yeast and selenium-enriched tea is determined. The total selenium in ordinary or selenium-enriched tea is determined by DAN fluorescence method. The results indicate that in selenium-enriched yeast about 20% of total selenium is present as SeC and in selenium-enriched tea SeC is the major form of selenoamino acids. The total selenium content in selenium-enriched tea soup is 0.09,,gSe/g accounting by 7% compared with that in selenium-enriched tea. Hence, only a little amount of selenium is utilized by drinking tea, and most selenium still stay in tealeaf. Uncertainty are 22.4% and 16.1% for determination of SeC in selenium-enriched yeast and selenium-enriched tea by differential pulse voltammetry (DPV) on (Se-Au)/GC electrode, respectively. [source]

Dose-dependent uptake, elimination, and toxicity of monosodium methanearsonate in adult zebra finches (Taeniopygia guttata)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2008
Courtney A. Albert
Abstract Monosodium methanearsonate (MSMA), an arsenic-based pesticide, has been used for the past 10 years in attempts to suppress mountain pine beetle (Dendroctonus ponderosae) outbreaks in British Columbia, Canada. Previous studies have shown that cavity nesting forest birds such as woodpeckers forage and breed in MSMA treated pine stands. Here we examined the effects of MSMA in the laboratory using the zebra finch (Taeniopygia guttata), with the objective to examine tissue distribution and sublethal toxic effects in a model avian species. Zebra finches were exposed to this pesticide at doses similar to those found in bark beetle samples from MSMA stands of trees treated in the southern interior of British Columbia (8, 24, and 72 ,g/g/d and a control group). Results showed high excretion (>90%) of arsenic in all dose groups, as well as dose-dependent trends in accumulation of arsenic in the blood (p < 0.001) and specific tissues. Monomethylarsonic acid, MMA (V), was the predominant form of arsenic in the blood plasma. Dimethylarsinic acid was the major form of arsenic found in the liver (83%) and kidney (61%) tissues. The brain tissue contained primarily the MMA (V) form (57%). Significant weight loss occurred in the two highest dose groups (p < 0.05). Birds in the highest dose group lost up to 15% of initial body mass. [source]

Analysis of hepatic vitamins A1, A2, their fatty acyl esters, and vitamin E for biomonitoring mammals feeding on freshwater fish

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002
Anne Käkelä
Abstract In tissues of freshwater fish,feeding mammals, 3,4-didehydroretinol (A2) is a major form of vitamin A. In mink liver, with organochlorine exposure, this analog has been found to decrease more than retinol (A1) and thus has potential as a sensitive freshwater biomarker. The presence of the analogs A1 and A2 as alcohol and different fatty acyl esters, which react to polychlorinated biphenyls differently, necessitates detailed analyses achieved by using direct extraction of tissue homogenate. In direct hexane extraction, compared to total levels of the vitamins obtained in the saponification procedure, a large proportion of the vitamins was released only after repeated and long-time vortex mixing with the extraction solvent. Thus, in tissue extraction, the use of internal standardization alone can lead to a rough underestimation of the levels of these fat-soluble vitamins. For analyses of vitamins A1 and A2 in liver, we applied the argentation high-performance liquid chromatography, which provided good separation of individual A1 and A2 fatty acyl esters. We report retention times for numerous esters of A1 and A2 and, to aid identification, the change in their retention properties after adding AgNO3 to the mobile phase. The argentation did not affect the recoveries of any forms of the retinoids studied but destroyed half the vitamin E. Despite selective acylation of fatty acids into the vitamin A esters, the fatty acids of the esters were the same as those found to be the major fatty acids in the gas,liquid chromatography of total lipids. The goal of this work was to create a methodology that is suitable for biomonitoring alcoholic and esterified vitamins A1 and A2 in tissues of freshwater fish,feeding mammals. [source]

Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2001
Brynjar Foss
Abstract: We investigated effects of Platelet-derived growth factor (PDGF) and Platelet factor 4 (PF-4) on the functional characteristics of native, human acute myelogenous leukemia (AML) blasts. AML blast expression of the PDGF-receptor ,-chain was detected for a subset of patients (45%), whereas PDGF-receptor ,-chain expression was detected for most patients (90%). Constitutive AML blast release of the PDGF-AB isoform (the major form also derived from normal platelets) was detected for 43% of patients, whereas PDGF-BB release was not detected for any patient. The PDGF isoforms AA, AB and BB had dose-dependent and divergent effects on spontaneous and cytokine-dependent AML blast proliferation, whereas for constitutive cytokine secretion (IL-1,, IL-6, TNF-,) inhibitory effects were rare and all three isoforms usually had no effect or enhanced the constitutive secretion. The PDGF effects were caused by a direct effect on the AML blasts and were not dependent on the presence of serum. The PDGF effects could also be detected after in vitro culture of AML cells in the presence of IL-4+granulocyte-macrophage colony stimulating factor. PF-4 had divergent effects on proliferation and cytokine secretion by native AML blasts. Our results suggest that exogenous (e.g. platelet-secreted) PDGF and PF-4 can function as regulators of leukemic hematopoiesis and possibly also modulate the function of residual AML cells in peripheral blood stem cell grafts. On the other hand, endogenous release of PDGF-AB by native blasts may modulate the function of normal cells in the bone marrow microenvironment (e.g. bone marrow stromal cells). [source]

Social biology of rodents

INTEGRATIVE ZOOLOGY (ELECTRONIC), Issue 4 2007
Jerry O. WOLFF
Abstract Herein, I summarize some basic components of rodent social biology. The material in this paper is summarized and condensed from a recent book "Rodent Societies: An Ecological and Evolutionary Perspective" edited by J. O. Wolff and P. W. Sherman (2007). I describe the four basic spacing patterns and illustrate how female territoriality is a function of offspring defense and male mating tactics are a function of female defensibility. The vulnerability of young to infanticide shapes female spacing and mating behavior. Food does not appear to be a defensible resource for rodents, except for those species that larder hoard nonperishable items such as seeds. Philopatry and the formation of kin groups result in genetic sub-structuring of the population, which in turn affects effective population size and genetic diversity. Dispersal is male biased and typically involves emigration from the maternal site to avoid female relatives and to seek unrelated mates. Scent marking is a major form of communication and is used in reproductive competition and to assess prospective mates, but it is also eavesdropped by predators to locate prey. Females do not appear to alter the sex ratio of litters in response to maternal condition but among arvicoline rodents daughters appear to be favored in spring and sons in autumn. Rodents are relatively monomorphic; however, females tend to be larger than males in the smallest species and smaller in the larger species. Predation risk results from an interaction among foraging time and vulnerability and in turn affects behavioral and life history characteristics. [source]

Relationships between expanding pinyon,juniper cover and topography in the central Great Basin, Nevada

JOURNAL OF BIOGEOGRAPHY, Issue 5 2008
Bethany A. Bradley
Abstract Aim, Increasing geographical range and density of conifers is a major form of land-cover change in the western United States, affecting fire frequency, biogeochemistry and possibly biodiversity. However, the extent and magnitude of the change are uncertain. This study aimed to quantify the relationship between changing conifer cover and topography. Location, The central Great Basin in the state of Nevada, USA. Methods, We used a series of Landsat Thematic Mapper satellite images from 1986, 1995 and 2005 to map change in pinyon,juniper woodlands (Pinus monophylla, Juniperus spp.) in the montane central Great Basin of Nevada. We derived fractional greenness for each year using spectral mixture analysis and identified all areas with an above average increase in greenness from 1986 to 1995 and 1995 to 2005. Results, Areas with high fractional greenness in 2005 were most likely to occur at elevations between 2200 and 2600 m a.s.l. Increases in fractional greenness between 1986 and 2005 were most likely to occur at elevations below 2000 m a.s.l. and on south-facing slopes. However, relationships between elevation and increasing greenness for individual mountain ranges varied considerably from the average trend. Fractional greenness values measured by Landsat suggest that the majority of pinyon,juniper woodlands have not reached their maximum potential tree cover. Main conclusions, Expansion of pinyon,juniper at low elevations and on south-facing slopes probably reflects increasing precipitation in the 20th century, higher water use efficiency caused by increasing atmospheric CO2 in the late 20th century and livestock grazing at the interface between shrubland and woodland. Identification of the spatial relationships between changing fractional greenness of pinyon,juniper woodland and topography can inform regional land management and improve projections of long-term ecosystem change. [source]

The diapause decision as a cascade switch for adaptive developmental plasticity in body mass in a butterfly

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 6 2010
K. GOTTHARD
Abstract Switch-induced developmental plasticity, such as the diapause decision in insects, is a major form of adaptation to variable environments. As individuals that follow alternative developmental pathways will experience different selective environments the diapause decision may evolve to a cascade switch that induces additional adaptive developmental differences downstream of the diapause decision. Here, we show that individuals following alternative developmental pathways in a Swedish population of the butterfly, Pararge aegeria, display differential optimization of adult body mass as a likely response to predictable differences in thermal conditions during reproduction. In a more northern population where this type of selection is absent no similar difference in adult mass among pathways was found. We conclude that the diapause decision in the southern population appears to act as a cascade switch, coordinating development downstream of the diapause decision, to produce adult phenotypes adapted to the typical thermal conditions of their expected reproductive period. [source]

Selective enhancement of the activity of C-terminally truncated, but not intact, acetylcholinesterase

JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
Martina Zimmermann
Abstract Acetylcholinesterase (AChE) is one of the fastest enzymes approaching the catalytic limit of enzyme activity. The enzyme is involved in the terminal breakdown of the neurotransmitter acetylcholine, but non-enzymatic roles have also been described for the entire AChE molecule and its isolated C-terminal sequences. These non-cholinergic functions have been attributed to both the developmental and degenerative situation: the major form of AChE present in these conditions is monomeric. Moreover, AChE has been shown to lose its typical characteristic of substrate inhibition in both development and degeneration. This study characterizes a form of AChE truncated after amino acid 548 (T548-AChE), whose truncation site is homologue to that of a physiological form of T-AChE detected in fetal bovine serum that has lost its C-terminal moiety supposedly due to proteolytic cleavage. Peptide sequences covered by this C-terminal sequence have been shown to be crucially involved in both developmental and degenerative mechanisms in vitro. Numerous studies have addressed the structure,function relationship of the AChE C-terminus with T548-AChE representing one of the most frequently studied forms of truncated AChE. In this study, we provide new insight into the understanding of the functional characteristics that T548-AChE acquires in solution: T548-AChE is incubated with agents of varying net charge and molecular weight. Together with kinetic studies and an analysis of different molecular forms and aggregation states of T548-AChE, we show that the enzymatic activity of T548-AChE, an enzyme verging at its catalytic limit is, nonetheless, apparently enhanced by up to 800%. We demonstrate, first, how the activity of T548-AChE can be enhanced through agents that contain highly positive charged moieties. Moreover, the un-competitive mechanism of activity enhancement most likely involves the peripheral anionic site of AChE that is reflected in delayed substrate inhibition being observed for activity enhanced T548-AChE. The data provides evidence towards a mechanistic and functional link between the form of AChE unique to both development and degeneration and a C-terminal peptide of T-AChE acting under those conditions. [source]

Hypoalgesia in mice lacking GABA transporter subtype 1

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2008
Yin Fang Xu
Abstract ,-Aminobutyric acid (GABA) transporters play a key role in the regulation of GABA neurotransmission. We reported previously that overexpression of the GABA transporter subtype 1 (GAT1), the major form of the GABA transporter in the CNS, led to hyperalgesia in mice. In the present study, nociceptive responses of GAT1-knockout mice (GAT1,/,) were compared with those of heterozygous (GAT+/,) and wild-type (GAT+/+) mice by four conventional pain models (tail-immersion test, hot-plate test, acetic acid,induced abdominal constriction test, and formalin test). In addition, the analgesic effects of two GAT1-selective inhibitors, NO-711 and tiagabine, were examined in all three genotypes using the same four models. Our data demonstrated that GAT1 deficiency because of genetic knockout or acute blockade by selective inhibitors leads to hypoalgesia in mice. These results confirmed the crucial role of GAT1 in the regulation of nociceptive threshold and suggested that GAT1 inhibitors have the potential for clinical use in pain therapy. © 2007 Wiley-Liss, Inc. [source]

Treatment of IgA nephropathy in children

NEPHROLOGY, Issue 2002
Norishige YOSHIKAWA
SUMMARY: IgA nephropathy is the most common primary glomerulonephritis in the world, and about 20,50% of patients develop progressive renal failure. the pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end-stage renal disease is also becoming apparent in children. This communication focuses on the treatment of IgA nephropathy in children. [source]

Taken into custody: girls and convent guardianship in Renaissance Florence

RENAISSANCE STUDIES, Issue 2 2003
Sharon T. Strocchia
This study examines the widespread practice of placing girls in the temporary care of convents in Renaissance Florence, a practice called serbanza. During the turbulent years from 1480 to 1530, guardianship became one of the most important social services offered by female religious communities, which sheltered girls in increasing numbers. Serbanza was the major form of extrafamilial care for young girls of the middling and artisan classes, as well as for the vulnerable rich, before the advent of large-scale custodial institutions in the later sixteenth century. Based on extensive archival records, this study documents how patterns of guardianship changed in response to political turmoil and concerns over female honour. I argue that convent guardianship formed part of the institutional and experiential foundation of female culture that cut across lines of neighbourhood and class, and introduced girls to a distinctive kind of constructed community. Boarding girls on a regular basis also raised important issues for internal monastic governance and ecclesiastical supervision. Nuns balanced the financial and social benefits of guardianship against the disruption of monastic routines and the disapproval of clerical officials. These tensions were resolved only by the reorganization of convent life and the development of new custodial institutions under Cosimo I. (pp. 177,200) [source]

Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 16 2010
Katharine A. Kenyon
Abstract Regulation of intracellular calcium is crucial both for proper neuronal function and survival. By coupling ATP hydrolysis with Ca2+ extrusion from the cell, the plasma membrane calcium-dependent ATPases (PMCAs) play an essential role in controlling intracellular calcium levels in neurons. In contrast to PMCA2 and PMCA3, which are expressed in significant levels only in the brain and a few other tissues, PMCA1 is ubiquitously distributed, and is thus widely believed to play a "housekeeping" function in mammalian cells. Whereas the PMCA1b splice variant is predominant in most tissues, an alternative variant, PMCA1a, is the major form of PMCA1 in the adult brain. Here, we use immunohistochemistry to analyze the cellular and subcellular distribution of PMCA1a in the brain. We show that PMCA1a is not ubiquitously expressed, but rather is confined to neurons, where it concentrates in the plasma membrane of somata, dendrites, and spines. Thus, rather than serving a general housekeeping function, our data suggest that PMCA1a is a calcium pump specialized for neurons, where it may contribute to the modulation of somatic and dendritic Ca2+ transients. J. Comp. Neurol. 518:3169,3183, 2010. © 2010 Wiley-Liss, Inc. [source]

Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 16 2010
Katharine A. Kenyon
Abstract Regulation of intracellular calcium is crucial both for proper neuronal function and survival. By coupling ATP hydrolysis with Ca2+ extrusion from the cell, the plasma membrane calcium-dependent ATPases (PMCAs) play an essential role in controlling intracellular calcium levels in neurons. In contrast to PMCA2 and PMCA3, which are expressed in significant levels only in the brain and a few other tissues, PMCA1 is ubiquitously distributed, and is thus widely believed to play a "housekeeping" function in mammalian cells. Whereas the PMCA1b splice variant is predominant in most tissues, an alternative variant, PMCA1a, is the major form of PMCA1 in the adult brain. Here, we use immunohistochemistry to analyze the cellular and subcellular distribution of PMCA1a in the brain. We show that PMCA1a is not ubiquitously expressed, but rather is confined to neurons, where it concentrates in the plasma membrane of somata, dendrites, and spines. Thus, rather than serving a general housekeeping function, our data suggest that PMCA1a is a calcium pump specialized for neurons, where it may contribute to the modulation of somatic and dendritic Ca2+ transients. J. Comp. Neurol. 518:3169,3183, 2010. © 2010 Wiley-Liss, Inc. [source]

Clear-cell adenofibroma can be a clonal precursor for clear-cell adenocarcinoma of the ovary: a possible alternative ovarian clear-cell carcinogenic pathway,

THE JOURNAL OF PATHOLOGY, Issue 1 2008
S Yamamoto
Abstract Several studies have reported that ovarian clear-cell adenocarcinoma can be derived from endometriosis. Although the clear-cell adenofibroma (CCAF), a major form of benign and borderline ovarian clear-cell tumour, has been suggested as another precursor for clear-cell adenocarcinoma (CCA), there is no supportive genetic evidence for this presumption. To examine the genetic linkage between CCAF and CCA of the ovary, we conducted allelotype analysis for both CCAF and adjacent CCA components in 14 cases of CCA associated with benign CCAF and/or borderline CCAF. DNA isolated from laser-microdissected tissue was subjected to polymerase chain reaction and analysis for loss of heterozygosity (LOH), using 17 polymorphic markers located on 11 chromosomal arms: 1p, 5q, 8p, 9p, 9q, 10q, 11q, 13q, 18q, 19p and 22q. For all informative loci, the frequency of LOH in adenocarcinoma was 49% (54/110 loci), and was significantly higher than those in the components of benign CCAF (22%, 20/92 loci) and borderline CCAF (30%, 25/83 loci) (,2 test; p < 0.05, respectively). The concordance rate in allelic patterns at all informative loci was 74% between benign CCAF and adenocarcinoma components, 81% between borderline CCAF and adenocarcinoma components, and 95% between benign CCAF and borderline CCAF components. Furthermore, between CCAF and adenocarcinoma components, an identical LOH pattern, involving the same alleles, was found in 13 (93%) of 14 cases at one or more chromosomal loci, and estimation of probability indicated that these events were very unlikely to have occurred by chance. Among the markers examined, LOHs on 5q, 10q and 22q were frequent in both CCAF and adenocarcinoma components, whereas LOHs on 1p and 13q were rare in CCAF components but frequent in adenocarcinoma components. These findings suggest that CCAF can be a clonal precursor for ovarian clear-cell adenocarcinoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Folinic acid,responsive seizures are identical to pyridoxine-dependent epilepsy,

ANNALS OF NEUROLOGY, Issue 5 2009
Renata C. Gallagher MD
Objective Folinic acid,responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to ,-aminoadipic semialdehyde (,-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid,responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders. Methods CSF samples were analyzed for the presence of ,-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Results Both patients reported here had increased CSF ,-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with ,-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid,responsive seizures showed similar results. Interpretation These results demonstrate that folinic acid,responsive seizures are due to ,-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid,responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with ,-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of ,-AASA in urine to identify this likely underdiagnosed and treatable disorder. Ann Neurol 2008 [source]

N,N,-Bis­[tris­(hydroxy­methyl)­methyl]­ethanedi­amide: six O,H,O hydrogen bonds generate only a two-­dimensional structure

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 8 2001
Jennifer N. Ross
Molecules of the title compound, C10H20N2O8, adopt a conformation which is almost centrosymmetric. The mol­ecules are disordered over two sets of sites with an occupancy ratio of 0.94:0.06. In the major form, there are two intramolecular O,H,O hydrogen bonds [O,O 2.756,(4) and 2.765,(4),Å; O,H,O 144 and 146°], in which the two amidic O atoms act as acceptors. In addition, there are four intermolecular O,H,O hydrogen bonds [O,O 2.650,(3),2.666,(3),Å; O,H,O 158,171°]; these link each mol­ecule to six others in a continuous sheet structure which contains five distinct ring motifs, two of the S(7) type, two of the R(10) type and one of the R(22) type. [source]

The release of leptin and its effect on hormone release from human pituitary adenomas

CLINICAL ENDOCRINOLOGY, Issue 6 2001
Márta Korbonits
BACKGROUND Leptin is the protein product of the obese gene, known to play an important role in body energy balance. The leptin receptor exists in numerous isoforms, the long isoform being the major form involved in signal transduction. Leptin expression has recently been demonstrated in the human pituitary, both in normal tissue and in pituitary adenomas. The long isoform of the leptin receptor has also been shown to be present in pituitary adenomas; however, contrasting results have been obtained regarding its expression in the normal human pituitary. AIM The aim of this study was (i) to investigate the presence and pattern of distribution of leptin mRNA and the long isoform of its receptor mRNA in the normal pituitary and in different types of pituitary adenomas with RT-PCR; (ii) to study leptin secretion from human pituitary tumours in culture and (iii) to assess in vitro pituitary hormone release following stimulation with human leptin. RESULTS Leptin receptor long isoform expression was detected in 2/4 GH-secreting adenomas, 12/17 non-functioning adenomas, 5/9 ACTH-secreting adenomas, 1/2 prolactinomas, 2/2 FSH-secreting adenomas and 5/5 normal pituitaries. The receptor long isoform did not segregate with any particular tumour type, and varying levels of expression were detected between the tissues studied. Leptin mRNA was detected at a low level of expression in 2/7 GH-secreting adenomas, 9/14 non-functioning adenomas, 2/3 ACTH-secreting adenomas, 1/3 prolactinomas and 1/3 FSH-secreting adenomas. We were unable to detect leptin mRNA in any of the five normal pituitaries removed at autopsy; however, immunostaining of a non-tumorous pituitary adjacent to an adenoma removed at transsphenoidal surgery showed scattered leptin positive cells. Culture of pituitary adenomas showed that 16/47 released leptin into the incubation media. Leptin release did not correlate with tumour type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumours caused stimulation of FSH and ,-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. CONCLUSION We conclude that not only is leptin stored within the pituitary, but it may also be released from pituitary cells and modulate other pituitary hormone secretion. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function. [source]

Activation of a calcium entry pathway by sodium pyrithione in the bag cell neurons of Aplysia

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2004
Ronald J. Knox
Abstract The ability of sodium pyrithione (NaP), an agent that produces delayed neuropathy in some species, to alter neuronal physiology was accessed using ratiometric imaging of cytosolic free Ca2+ concentration ([Ca2+]i) in fura PE-filled cultured Aplysia bag cell neurons. Bath-application of NaP evoked a [Ca2+]i elevation in both somata and neurites with an EC50 of ,300 nM and a Hill coefficient of ,1. The response required the presence of external Ca2+, had an onset of 3,5 min, and generally reached a maximum within 30 min. 2-Methyl-sulfonylpyridine, a metabolite and close structural analog of NaP, did not elevate [Ca2+]i. Under whole-cell current-clamp recording, NaP produced a ,14 mV depolarization of resting membrane potential that was dependent on external Ca2+. These data suggested that NaP stimulates Ca2+ entry across the plasma membrane. To minimize the possibility that a change in cytosolic pH was the basis for NaP-induced Ca2+ entry, bag cell neuron intracellular pH was estimated with the dye 2,,7,-bis(carboxyethyl-5(6)-carboxy-fluorescein acetoxy methylester. Exposure of the neurons to NaP did not alter intracellular pH. The slow onset and sustained nature of the NaP response suggested that a cation exchange mechanism coupled either directly or indirectly to Ca2+ entry could underlie the phenomenon. However, neither ouabain, a Na+/K+ ATPase inhibitor, nor removal of extracellular Na+, which eliminates Na+/Ca2+ exchanger activity, altered the NaP-induced [Ca2+]i elevation. Finally, the possibility that NaP gates a Ca2+ -permeable ion channel in the plasma membrane was examined. NaP did not appear to activate two major forms of bag cell neuron Ca2+ -permeable ion channels, as Ca2+ entry was unaffected by inhibition of voltage-gated Ca2+ channels using nifedipine or by inhibition of a voltage-dependent, nonselective cation channel using a high concentration of tetrodotoxin. In contrast, two potential store-operated Ca2+ entry current inhibitors, SKF-96365 and Ni2+, attenuated NaP-induced Ca2+ entry. We conclude that NaP activates a slow, persistent Ca2+ influx in Aplysia bag cell neurons. © 2004 Wiley Periodicals, Inc. J Neurobiol 411,423, 2004 [source]

Regulated expression and intracellular localization of cystatin F in human U937 cells

FEBS JOURNAL, Issue 22 2002
Carl-Michael Nathanson
Cystatin F is a cysteine peptidase inhibitor recently discovered in haematopoietic cells by cDNA cloning. To further investigate the expression, distribution and properties of the native human inhibitor the promyeloid cell line U937 has been studied. The cells expressed relatively large quantities of cystatin F, which was found both secreted and intracellularly. The intracellular levels were unusually high for a secreted cystatin (, 25% of the cystatin F in 2- or 4-day culture medium). By contrast, U937 cells contained only 3,4% of the related inhibitor, cystatin C. Cystatin F purified from lysates of U937 cells showed three major forms carrying two, one or no carbohydrate chains. Immunocytochemistry demonstrated a marked cytoplasmic cystatin F staining in a granular pattern. Double staining with a marker for endoplasmic reticulum revealed no colocalization for cystatin F. Analysis of the promoter region of the cystatin F gene (CST7) showed that it, like that of the cystatin C gene (CST3), is devoid of typical TATA- and CAAT-box elements. In contrast to the cystatin C promoter, it does not contain multiple Sp1 binding sites, but has a unique site for C/EBP,, possibly explaining the restricted expression of the cystatin F gene. Cells stimulated with all- trans retinoic acid to differentiate them towards a granulocytic pathway, showed a strong (, 18-fold) down-regulation of intracellular cystatin F and almost abolished secreted levels of the inhibitor. Stimulation with tetradecanoyl phorbol acetate, causing monocytic differentiation, also resulted in down-regulation (two fold to threefold) of cystatin F expression, whereas the cystatin C expression was essentially unaltered in both experiments. The results suggest that cystatin F as an intracellular cysteine peptidase inhibitor with readily regulated expression, may be a candidate to control the cysteine peptidase activity known to be essential for antigen presentation in different blood cell lineages. [source]

Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains

GENES TO CELLS, Issue 10 2004
Takeshi Tenno
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves as a signalling function that controls a wide variety of cellular processes. To date, two major forms of polyubiquitin chain have been functionally characterized, in which the isopeptide bond linkages involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to target proteins for degradation by the proteasome, whereas Lys63-linked polyubiquitination has been linked to numerous cellular events that do not rely on degradative signalling via the proteasome. Apparently linkage-specific conformations of polyubiquitin chains are important for these cellular functions, but the structural bases distinguishing Lys48- and Lys63-linked chains remain elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48-linked chains, Lys63-linked chains are elongated molecules with no stable non-covalent intersubunit interfaces and thus adopt a radically different conformation from that of Lys48-linked chains. [source]

Signal transducers and activators of transcription 3 signaling pathway.

INFLAMMATORY BOWEL DISEASES, Issue 2 2005
An Essential Mediator of Inflammatory Bowel Disease, Other Forms of Intestinal Inflammation
Abstract Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation. [source]

BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML)

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2002
R.M. Arana-Trejo
There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph,. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML. [source]

Clinical and molecular characterization of chronic hepatitis B in Albania: A country that is still highly endemic for HBV infection

JOURNAL OF MEDICAL VIROLOGY, Issue 1 2005
L.A. Kondili
Abstract Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg-positive and HBeAg-negative chronic hepatitis B). A cross-sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV-DNA was measured with an in-house PCR with a sensitivity of 104 copies/ml which uses primers encompassing the pre-core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg-negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti-HBe-positive and older patients. In more than 90% of the HBeAg-negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre-core mutation at nucleotide 1896 was found. Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver-disease patients, the age of peak prevalence was at least 10 years lower for HBeAg-positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level. J. Med. Virol. 75:20,26, 2005. © 2005 Wiley-Liss, Inc. [source]

Novel elicitin-like proteins isolated from the cell wall of the biocontrol agent Pythium oligandrum induce defence-related genes in sugar beet

MOLECULAR PLANT PATHOLOGY, Issue 5 2006
SHIGEHITO TAKENAKA
SUMMARY We previously reported that cell wall protein fractions (CWPs) of the biocontrol agent Pythium oligandrum have elicitor properties in sugar beet and wheat. Here we have examined the effect of treatment with the D -type of CWP, a fraction that contains two major forms (POD-1 and POD-2), on the induction of defence-related genes in sugar beet. Using PCR-based cDNA library subtraction, we identified five genes that were highly expressed in response to CWP treatment. The five genes are probably of oxalate oxidase-like germin (OxOLG), glutathione S-transferase (GST), 5-enol-pyruvylshikimate-phosphate synthase (EPSPS), phenylalanine ammonia-lyase (PAL) and aspartate aminotransferase (AAT). In addition, we purified and characterized POD-1 and POD-2 and found that POD-1 induced all five genes, whereas POD-2 induced three of the genes, but not OxOLG or GST. A sugar beet bioassay indicated that CWP, POD-1 and POD-2 are each sufficient to induce resistance to sugar beet seedling disease caused by Aphanomyces cochlioides. Although carbohydrate analyses indicated that POD proteins were glycoproteins with similar carbohydrate compositions, containing approximately 15.0% carbohydrate by weight, their peptide portions have elicitor activity. Furthermore, cDNAs of POD-1 and POD-2 proteins were cloned, and the deduced amino acid sequences were found to be 82.9% identical. Characterization of their molecular structures indicated that they have an elicitin domain followed by a C-terminal domain with a high frequency of Ser, Thr, Ala and Pro, which is structurally similar to class III elicitins. However, phylogenetic analysis with 22 representative elicitin and elicitin-like proteins showed that POD-1 and POD-2 are distinct from previously defined elicitin and elicitin-like proteins. Therefore, POD-1 and POD-2 are novel oomycete cell wall elicitin-like glycoproteins. [source]

Is There a Genetic Basis for Health Disparities in Human Immunodeficiency Virus Disease?

MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010
Cheryl Winkler PhD
Abstract The highest global prevalence rates for human immunodeficiency virus and acquired immune deficiency syndrome have been recorded in southern Africa; in the United States, individuals of African descent are disproportionately affected by human immunodeficiency virus infection. Human immunodeficiency virus,infected individuals with African ancestry are also estimated to have a 17-fold or greater risk for developing human immunodeficiency virus,associated nephropathy in comparison with their counterparts of non-African descent. Several recent studies have implicated genetic alleles that are more frequent in populations of African descent and increase the risk of human immunodeficiency virus infection and the risk of human immunodeficiency virus,associated neuropathy (HIVAN). The supposition that persons of African descent are more susceptible to human immunodeficiency virus infection because of an underlying genetic predisposition is not supported by available evidence. However, strong, replicated data show that the increased risk for human immunodeficiency virus,associated nephropathy, as well as other major forms of kidney disease in individuals of African descent, is due in part to MYH9 (myosin, heavy chain 9, non-muscle) renal disease susceptibility alleles that are very frequent throughout sub-Saharan Africa but are infrequent or absent in non-Africans. Selection, drift, and demographic events shape the allelic architecture of the human genome: it is expected that these events will be reflected in geographic-specific differentiation in allele frequencies for a small subset of alleles that may be associated with either increased or reduced risk for complex and infectious diseases. Mt Sinai J Med 77:149,159, 2010. © 2010 Mount Sinai School of Medicine [source]

Inflammatory myopathies: Clinical, diagnostic and therapeutic aspects

MUSCLE AND NERVE, Issue 4 2003
Frank L. Mastaglia MD
Abstract The three major forms of immune-mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis-specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine-based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions. Muscle Nerve 27:407,425, 2003 [source]

Association of interleukin-1, polymorphism with recurrent aphthous stomatitis in Brazilian individuals

ORAL DISEASES, Issue 6 2006
ALS Guimarães
Background:, Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of oral ulceration in an otherwise healthy individual. Some reports in the literature indicate that RAS may have immunological, psychological, genetic and microbiological bases. The purpose of the present study was to investigate the possible association between interleukin-1, (IL-1,) +3954 (C/T) genetic polymorphism and RAS in a sample of Brazilian patients. Subjects and methods:, Sixty-two consecutive subjects affected by minor and major forms of RAS and 62 healthy volunteers were genotyped at IL-1, (+3954). The chi-squared test was used for statistical analysis. Results:, A significant increase in the high production of IL-1, genotype CT was observed in the group with RAS (P = 0.01). After stratifying RAS patients according to the mean number of lesions per episode, a significant difference was only observed between patients with ,3 lesions in each episode and control. Conclusion:, There is an increased frequency of polymorphism associated with high IL-1, production in RAS patients. [source]

Paracetamol (Acetaminophen): mechanisms of action

PEDIATRIC ANESTHESIA, Issue 10 2008
BRIAN J. ANDERSON PhD FANZCA FJFICM
Summary Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H2 synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH2. The two major forms of this enzyme are the constitutive PGHS-1 and the inducible PGHS-2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG2 is dependent on a tyrosine-385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe3+ at the POX site is essential for conversion of tyrosine-385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG2. Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti-inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p -aminophenol). p -Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase. [source]

Democratisation and corruption in Mongolia

PUBLIC ADMINISTRATION & DEVELOPMENT, Issue 3 2007
Verena Fritz
Abstract More democratic and open systems of government are generally assumed to contain corruption. Subsequent to the end of the communist system in 1990, Mongolia has established a democratic regime, and has been assessed as being relatively well governed. However, more recently, corruption has been worsening, despite the continuation of a democratic regime. This article inquires into the drivers of corruption and into the reasons for why accountability has not been more effective despite a democratic form of government. The availability of three major forms of rents,foreign aid, privatisation and natural resource extraction,is discussed as important drivers. The recent mining boom appears to have reinforced weaknesses in Mongolia's system of accountability. Underlying weaknesses include certain communist legacies, especially of intransparent government and of a ,dependent' judicial system, and substantially increased inequality as a result of transition. Copyright © 2007 John Wiley & Sons, Ltd. [source]